This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The primary objective of this exploratory study is to examine the binding of protein molecules, both amyloid and tau, in the brain using positron emission tomography (PET) with fluorinated analog of 1, 1-dicyano-2-[6- (dimethylamino)-2-naphthalenyl] propene ([18F]FDDNP) in patients with late life major depression (MDD) and healthy controls. An additional goal is to examine the relationship of [18F]FDDNP binding, both globally and regionally, to specific measures of cognition (global cognition and measures of executive function and recall). Depression in late-life is both a risk factor and a prodrome for dementia, especially dementia of the Alzheimer Type (AD). FDDNP is a valid in vivo probe that binds to protein, both amyloid and tau (core biochemical components of neuritic plaques and neurofibrillary tangles in the brain respectively). FDDNP binding is higher in patients diagnosed with AD and mild cognitive impairment (MCI) when compared with control subjects and in vivo binding correlates well with post mortem evidence of neuropathology. Our proposal will help us cross- sectionally examine overall protein burden and its relationship to cognitive performance in patients with MDD. This preliminary project will lead to longitudinal studies that examine the relationship of FDDNP binding to long term clinical outcome and a comparison of binding patterns in MDD to patients diagnosed with probable AD. Our observations will have important implications for the neurobiology of mood and cognitive disorders in the elderly. 7. Project Narrative The study will help identify patients with late-life depression who may be 'at risk'for developing dementia of the Alzheimer Type over time. This will facilitate the early identification of patients who may benefit from aggressive therapy aimed at alleviating both mood and cognitive symptoms.